Optical imaging is a versatile and widely used visualization modality in modern medical research and clinical practice. The past few decades have witnessed an explosion in the development of various optical imaging technologies that currently exist. Fluorescence imaging (FLI) has been vastly improved to provide insight into the cellular structure and organization with a spatial resolution approaching that of electron microscopy. Optical coherence tomography (OCT), a twenty-year old technique that is based on low-coherence interferometry, enables the visualization of subsurface anatomic structures of biological tissue with a resolution down to a few microns. In the past decade, photoacoustic imaging (PAI) has emerged as a promising medical imaging modality to delineate microvasculature and tissue physiological/functional parameters non-invasively at ultrasound resolution. All these imaging modalities have been successfully applied endoscopically for noninvasive and high resolution imaging of various internal structures and organs, such as the brain, gastrointestinal tract, vasculature, digestive tract, cervix, colon, bladder, ovary, kidney, etc. However, individually, these imaging modalities do not provide sufficient information to get an accurate clinical diagnosis, such as a cancerous development.
Recent years have also seen increasing research and development focused on integration of multiple imaging modalities into a single high resolution fiber optic endoscope [See Bedard, N., M. Pierce, A. El-Nagger, S. Anandasabapathy, A. Gillenwater, and R. Richards-Kortum, Emerging roles for multimodal optical imaging in early cancer detection: a global challenge. Technol Cancer Res Treat, 2010. 9(2): p. 211-7; and Boppart, S. A., T. F. Deutsch, and D. W. Rattner, Optical imaging technology in minimally invasive surgery. Current status and future directions. Surg Endosc, 1999. 13(7): p. 718-22].
Yang et al., reported the integration of OCT, ultrasound and PAI into a 5-mm endoscope for ovarian tissue characterization [See Yang, Y., X. Li, T. Wang, P. D. Kumavor, A. Aguirre, K. K. Shung, Q. Zhou, M. Sanders, M. Brewer, and Q. Zhu, Integrated optical coherence tomography, ultrasound and photoacoustic imaging for ovarian tissue characterization. Biomed Opt Express, 2011. 2(9): p. 2551-61].
Li et al., developed an all-fiber-optic endoscopy platform using a double-clad fiber for simultaneous OCT and fluorescence imaging [See Mavadia, J., J. Xi, Y. Chen, and X. Li, An all-fiber-optic endoscopy platform for simultaneous OCT and fluorescence imaging. Biomed Opt Express, 2012. 3(11): p. 2851-9; and Xi, J., Y. Chen, Y. Zhang, K. Murari, M. J. Li, and X. Li, Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging. Opt Lett, 2012. 37(3): p. 362-4].
Shao et al, designed an integrated microendoscopy system combining photoacoustic and fluorescence microscopy for visualizing fluorescently labeled cellular components and optically absorbing microvasculature simultaneously [See Shao, P., W. Shi, P. Hajireza, and R. J. Zemp, Integrated micro-endoscopy system for simultaneous fluorescence and optical-resolution photoacoustic imaging. J Biomed Opt, 2012. 17(7): p. 076024].
Yang et al., presented simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo [See Yang, J. M., C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, and L. V. Wang, Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo. Nat Med, 2012. 18(8): p. 1297-1302].
Most of the existing multimodal endoscopic imaging systems combine two imaging modalities, and, only a few attempts have been made to integrate all three modalities into a single fiber optic endoscope.
These existing multimodality techniques often require mechanical scanning at the distal end of the probe, which is challenging largely due to the size constraints and is often incompatible with widely used whole body imaging procedures, such as magnetic resonance imaging (MRI) and computerized tomography (CT). A major difficulty in developing a multimodality endoscope that includes PAI is to design an ultrasonic detector array that fits a tight space with enough detection bandwidth and sensitivity for the recovery of weak photoacoustic signals. In addition, a compact endoscopic imaging platform that accommodates or can be easily modified for all three imaging modalities has not been reported. The ability to provide complimentary, high resolution images about tissue structural, functional and molecular information with a single endoscope would substantially improve the sensitivity and specificity in diagnosis and characterization of a variety of disorders, such as the detection of pre-cancers lesions and cancers.